Effect of 5-HT7 antagonist SB-269970 in the modulation of working and reference memory in the rat

Gasbarri, Antonella; Cifariello, Agata; Pompili, Assunta; Meneses, Alfredo

doi:10.1016/j.bbr.2007.12.020

Cited by 80 publications

(50 citation statements)

References 77 publications

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“…Thus, SB269970 improved reference memory in a radial arm maze (Gasbarri et al, 2008) and a PCPinduced reversal learning deficit in rats (McLean et al, 2009). Consistent with these reports, several studies have demonstrated a procognitive effect of 5-HT 7 antagonists (see Discussion).…”

Section: Introductionsupporting

confidence: 78%

The Role of 5-Hydroxytryptamine 7 Receptors in the Phencyclidine-Induced Novel Object Recognition Deficit in Rats

Horiguchi

Huang²,

Meltzer³

2011

J Pharmacol Exp Ther

120

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The role of 5-hydroxytryptamine (serotonin) (5-HT) 7 receptor antagonism in the actions of atypical antipsychotic drugs (APDs), e.g., amisulpride, clozapine, and lurasidone, if any, is uncertain. We examined the ability of 5-HT 7 receptor antagonism alone and as a component of amisulpride and lurasidone to reverse deficits in rat novel object recognition (NOR) produced by subchronic treatment with the N-methyl-D-aspartate receptor antagonist phencyclidine (PCP), and we examined the ability of supplemental 5-HT 7 antagonism to augment the inability of sulpiride, haloperidol, and (1R,4R,5S,6R)-4-amino-2-oxabicyclo[3.1.0]hexane-4,6-dicarboxylic acid (LY379268), a metabotropic glutamate receptor (mGluR) 2/3 agonist, which lack 5-HT 7 antagonism, to reverse the NOR deficit. The 5-HT 7 receptor antagonist, (2R)-1-[(3-hydroxyphenyl)sulfonyl]-2-[2-(4-methyl-1-piperidinyl)ethyl]pyrrolidine (SB269970) (0.1-1 mg/kg) dose-dependently reversed PCP-induced NOR deficits. In addition, the ability of lurasidone (0.1 mg/kg) and amisulpride (3 mg/kg) to reverse this deficit was blocked by cotreatment with the 5-HT 7 receptor agonist (2S)-(ϩ)-5-(1,3,5-trimethylpyrazol-4-yl)-2-(dimethylamino)tetralin (AS19) (5-10 mg/kg), which did not affect NOR in naive rats. Sulpiride, a less potent 5-HT 7 antagonist than amisulpride, did not itself improve the PCPinduced NOR deficit. However, a subeffective dose of SB269970 (0.1 mg/kg) in combination with subeffective doses of lurasidone (0.03 mg/kg), amisulpride (1 mg/kg), or sulpiride (20 mg/kg), also reversed the PCP-induced NOR deficit. Pimavanserin, a 5-HT 2A inverse agonist, LY379268, and haloperidol did not potentiate the ability of subeffective SB269970 to improve the NOR deficit. Furthermore, the mGluR2/3 antagonist (2S)-2-amino-2-[(1S,2S)-2-carboxycycloprop-1-yl]-3-(xanth-9-yl)propanoic acid (LY341495), which blocks the effect of clozapine to reverse the NOR deficit, did not block the SB269970-induced amelioration of the NOR deficit. These results suggest 5-HT 7 antagonism may contribute to the efficacy of some atypical APDs in the treatment of cognitive impairment in schizophrenia and may itself have some benefit in this regard.

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Section: Introductionsupporting

confidence: 78%

The Role of 5-Hydroxytryptamine 7 Receptors in the Phencyclidine-Induced Novel Object Recognition Deficit in Rats

Horiguchi

Huang²,

Meltzer³

2011

J Pharmacol Exp Ther

120

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“…A growing body of evidence supports the concept for targeting 5-HT 7 antagonism as a possible mechanism for the treatment of cognitive deficits and a potential target for novel anxiolytic and antidepressant drugs (Hedlund et al, 2005;Abbas et al, 2009;Mnie-Filali et al, 2009;Horiguchi et al, 2011). In conclusion, the results reported here suggest that the procognitive effect of 5-HT 7 receptor antagonism (Gasbarri et al, 2008;Horiguchi et al, 2011) may result from enhancement of NMDAR function.…”

Section: Discussionsupporting

confidence: 65%

“…5-HT 7 expression and function also correlate with neuronal depolarization in the developing rat PFC (Béïque et al, 2004). 5-HT 7 receptor knockout or blockade of the 5-HT 7 receptor enhances learning and memory (Gasbarri et al, 2008). A growing body of evidence supports the concept for targeting 5-HT 7 antagonism as a possible mechanism for the treatment of cognitive deficits and a potential target for novel anxiolytic and antidepressant drugs (Hedlund et al, 2005;Abbas et al, 2009;Mnie-Filali et al, 2009;Horiguchi et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

The Novel Antipsychotic Drug Lurasidone Enhances N-Methyl-d-aspartate Receptor-Mediated Synaptic Responses

Yuen

Wei

et al. 2011

Mol Pharmacol

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N-Methyl-D-aspartate (NMDA) receptor (NMDAR) hypofunctionhas been postulated to contribute to the cognitive deficit of schizophrenia. In this study, we examined the effect of lurasidone (Latuda; Dainippon Sumitomo Pharma Co. Ltd., Tokyo, Japan), a newly approved atypical antipsychotic drug (APD), on NMDAR synaptic function in rat frontal cortical pyramidal neurons. In vivo administration of lurasidone produced a significant and selective enhancement of NMDAR-mediated synaptic responses and surface expression of NR2A and NR2B subunits. Lurasidone has high affinity for serotonin 5-HT 1A , 5-HT 2A , and 5-HT 7 receptors and dopamine D 2 receptors. In vivo administration of the 5-HT 7 receptor antagonist (2R)-1-[(3-hydroxyphenyl)sulfonyl]-2 -(2-(4-methyl-1-piperidinyl)ethyl)pyrrolidine (SB-269970) mimicked the enhancing effect of lurasidone on NMDAR responses, whereas the D 2 receptor antagonist haloperidol failed to do so. Previous studies have found that shortterm administration of lurasidone reverses the cognitive impairment induced by subchronic administration of phencyclidine (PCP), an NMDAR noncompetitive antagonist. In this study, we found that lurasidone, as well as the prototypical atypical APD clozapine, restored NMDAR-mediated synaptic responses to normal levels in the PCP model of schizophrenia. These results suggest that NMDAR is the potential key molecular target of lurasidone, possibility via antagonizing 5-HT 7 receptors, which is consistent with evidence that 5-HT 7 receptor antagonism contributes to cognitive enhancement by atypical APDs in patients with schizophrenia.

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“…The involvement of 5-HT7R in fear conditioning has been demonstrated in 5-HT7R KO mice, which displayed impaired contextual fear conditioning along with decreased longterm synaptic plasticity within the CA1 region of the hippocampus (Roberts et al, 2004). Based on preclinical findings, 5-HT7Rs are now emerging as a possible therapeutic target for the treatment of cognitive disorders and depression (Gasbarri et al, 2008, Matthys et al, 2011and Volpicelli et al, 2014. For example, treatment with selective 5-HT7R antagonists has been shown to have anxiolitic and antidepressant effects in mice tested in the forced swim and tail suspension tests (Nikiforuk, 2015).…”

Section: Functional Implicationsmentioning

confidence: 99%

The 5-HT7 receptor triggers cerebellar long-term synaptic depression via PKC-MAPK

et al. 2016

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The 5-HT7 receptor (5-HT7R) mediates important physiological effects of serotonin, such as memory and emotion, and is emerging as a therapeutic target for the treatment of cognitive disorders and depression. Although previous studies have revealed an expression of 5-HT7R in cerebellum, particularly at Purkinje cells, its functional role and signaling mechanisms have never been described. Using patch-clamp recordings in cerebellar slices of adult mice, we investigated the effects of a selective 5-HT7R agonist, LP-211, on the main plastic site of the cerebellar cortex, the parallel fiber-Purkinje cell synapse. Here we show that 5-HT7R activation induces long-term depression of parallel fiber-Purkinje cell synapse via a postsynaptic mechanism that involves the PKC-MAPK signaling pathway. Moreover, a 5-HT7R antagonist abolished the expression of PF-LTD, produced by pairing parallel fiber stimulation with Purkinje cell depolarization; whereas, application of a 5-HT7R agonist impaired LTP induced by 1 Hz parallel fiber stimulation. Our results indicate for the first time that 5-HT7R exerts a fine regulation of cerebellar bidirectional synaptic plasticity that might be involved in cognitive processes and neuropsychiatric disorders involving the cerebellum

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Effect of 5-HT7 antagonist SB-269970 in the modulation of working and reference memory in the rat

Cited by 80 publications

References 77 publications

The Role of 5-Hydroxytryptamine 7 Receptors in the Phencyclidine-Induced Novel Object Recognition Deficit in Rats

The Role of 5-Hydroxytryptamine 7 Receptors in the Phencyclidine-Induced Novel Object Recognition Deficit in Rats

The Novel Antipsychotic Drug Lurasidone Enhances N-Methyl-d-aspartate Receptor-Mediated Synaptic Responses

The 5-HT7 receptor triggers cerebellar long-term synaptic depression via PKC-MAPK

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